Effect of a High-Fat Diet and Metformin on Placental mTOR Signaling in Mice

Abstract Objective This study was aimed to measure the effects of a high-fat diet and metformin on placental mechanistic target of rapamycin (mTOR) signaling in mice. Study Design Pregnant friend virus B (FVB)-strain mice were allocated on embryonic day (e) 0.5 to one of fo...

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Main Authors: Matthew R. Grace, Sarah K. Dotters-Katz, Chunxiao Zhou, Tracy Manuck, Kim Boggess, Victoria Bae-Jump
Format: Article
Language:English
Published: Thieme Medical Publishers, Inc. 2019-04-01
Series:American Journal of Perinatology Reports
Subjects:
Online Access:http://www.thieme-connect.de/DOI/DOI?10.1055/s-0039-1683362
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author Matthew R. Grace
Sarah K. Dotters-Katz
Chunxiao Zhou
Tracy Manuck
Kim Boggess
Victoria Bae-Jump
author_facet Matthew R. Grace
Sarah K. Dotters-Katz
Chunxiao Zhou
Tracy Manuck
Kim Boggess
Victoria Bae-Jump
author_sort Matthew R. Grace
collection DOAJ
description Abstract Objective This study was aimed to measure the effects of a high-fat diet and metformin on placental mechanistic target of rapamycin (mTOR) signaling in mice. Study Design Pregnant friend virus B (FVB)-strain mice were allocated on embryonic day (e) 0.5 to one of four groups; group 1: control diet (CD, 10% fat) + control treatment (CT), group 2: CD + metformin treatment (MT), group 3: high-fat diet (HFD, 60% fat) + CT, and group 4: HFD + MT. Metformin (2.5 mg/mL) was provided in water; CT mice received water. Fetuses and placentas were collected. Western blot measured placental p-Akt and p-S6 expression. Results 20 dams (five/group) and 192 fetuses were studied. Compared with CD-fed, HFD-fed dams had higher placental p-Akt protein expression (p < 0.0001). Among HFD-dams, placental p-Akt was higher in metformin-treated compared with control-treated (p < 0.001). Among CD-fed dams, there was no significant difference in placental p-S6 expression in MT versus CT groups. Among HFD-fed dams placental p-S6 expression was lower in those exposed to metformin-treated versus controls (p = 0.001). Conclusion Increased placental mTOR signaling and metformin inhibition of placental mTOR signaling only occurred in the presence of an HFD exposure. These findings suggest that metformin may modulate placental mTOR signaling in the presence of metabolic exposures during pregnancy.
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spelling doaj.art-0a55b23d496f4ffaa704678b8f3edfe82022-12-22T00:44:43ZengThieme Medical Publishers, Inc.American Journal of Perinatology Reports2157-69982157-70052019-04-010902e138e14310.1055/s-0039-1683362Effect of a High-Fat Diet and Metformin on Placental mTOR Signaling in MiceMatthew R. Grace0Sarah K. Dotters-Katz1Chunxiao Zhou2Tracy Manuck3Kim Boggess4Victoria Bae-Jump5Tennessee Maternal Fetal Medicine and the University of Tennessee, Division of Obstetrics and Gynecology, Department of Clinical Medicine Education, Nashville, TennesseeDivision of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Duke University, Durham, North CarolinaDivision of Gynecologic Oncology, University of North Carolina School of Medicine, Chapel Hill, North CarolinaDivision of Maternal–Fetal Medicine, Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, North CarolinaDivision of Maternal–Fetal Medicine, Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, North CarolinaDivision of Gynecologic Oncology, University of North Carolina School of Medicine, Chapel Hill, North CarolinaAbstract Objective This study was aimed to measure the effects of a high-fat diet and metformin on placental mechanistic target of rapamycin (mTOR) signaling in mice. Study Design Pregnant friend virus B (FVB)-strain mice were allocated on embryonic day (e) 0.5 to one of four groups; group 1: control diet (CD, 10% fat) + control treatment (CT), group 2: CD + metformin treatment (MT), group 3: high-fat diet (HFD, 60% fat) + CT, and group 4: HFD + MT. Metformin (2.5 mg/mL) was provided in water; CT mice received water. Fetuses and placentas were collected. Western blot measured placental p-Akt and p-S6 expression. Results 20 dams (five/group) and 192 fetuses were studied. Compared with CD-fed, HFD-fed dams had higher placental p-Akt protein expression (p < 0.0001). Among HFD-dams, placental p-Akt was higher in metformin-treated compared with control-treated (p < 0.001). Among CD-fed dams, there was no significant difference in placental p-S6 expression in MT versus CT groups. Among HFD-fed dams placental p-S6 expression was lower in those exposed to metformin-treated versus controls (p = 0.001). Conclusion Increased placental mTOR signaling and metformin inhibition of placental mTOR signaling only occurred in the presence of an HFD exposure. These findings suggest that metformin may modulate placental mTOR signaling in the presence of metabolic exposures during pregnancy.http://www.thieme-connect.de/DOI/DOI?10.1055/s-0039-1683362metforminmtormicehigh-fat diet
spellingShingle Matthew R. Grace
Sarah K. Dotters-Katz
Chunxiao Zhou
Tracy Manuck
Kim Boggess
Victoria Bae-Jump
Effect of a High-Fat Diet and Metformin on Placental mTOR Signaling in Mice
American Journal of Perinatology Reports
metformin
mtor
mice
high-fat diet
title Effect of a High-Fat Diet and Metformin on Placental mTOR Signaling in Mice
title_full Effect of a High-Fat Diet and Metformin on Placental mTOR Signaling in Mice
title_fullStr Effect of a High-Fat Diet and Metformin on Placental mTOR Signaling in Mice
title_full_unstemmed Effect of a High-Fat Diet and Metformin on Placental mTOR Signaling in Mice
title_short Effect of a High-Fat Diet and Metformin on Placental mTOR Signaling in Mice
title_sort effect of a high fat diet and metformin on placental mtor signaling in mice
topic metformin
mtor
mice
high-fat diet
url http://www.thieme-connect.de/DOI/DOI?10.1055/s-0039-1683362
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